Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 28 June 2002:
Vol. 296. no. 5577, pp. 2410 - 2413
DOI: 10.1126/science.1070104
Prev | Table of Contents

Reports

Correction of ADA-SCID by Stem Cell Gene Therapy Combined with Nonmyeloablative Conditioning

Alessandro Aiuti,1 Shimon Slavin,2 Memet Aker,2 Francesca Ficara,1 Sara Deola,1 Alessandra Mortellaro,1 Shoshana Morecki,2 Grazia Andolfi,1 Antonella Tabucchi,3 Filippo Carlucci,3 Enrico Marinello,3 Federica Cattaneo,1 Sergio Vai,1 Paolo Servida,4 Roberto Miniero,5 Maria Grazia Roncarolo,16* Claudio Bordignon16*dagger

Hematopoietic stem cell (HSC) gene therapy for adenosine deaminase (ADA)-deficient severe combined immunodeficiency (SCID) has shown limited clinical efficacy because of the small proportion of engrafted genetically corrected HSCs. We describe an improved protocol for gene transfer into HSCs associated with nonmyeloablative conditioning. This protocol was used in two patients for whom enzyme replacement therapy was not available, which allowed the effect of gene therapy alone to be evaluated. Sustained engraftment of engineered HSCs with differentiation into multiple lineages resulted in increased lymphocyte counts, improved immune functions (including antigen-specific responses), and lower toxic metabolites. Both patients are currently at home and clinically well, with normal growth and development. These results indicate the safety and efficacy of HSC gene therapy combined with nonmyeloablative conditioning for the treatment of SCID.

1 San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Milan, Italy.
2 Departments of Bone Marrow Transplantation and Pediatrics, Hadassah University Hospital, Jerusalem, Israel.
3 Institute of Biochemistry and Enzymology, University of Siena, Siena, Italy.
4 BMT and Gene Therapy Program, Scientific Institute H. S. Raffaele;
5 Department of Biological and Clinical Science, University of Turin, Turin, Italy.
6 Università Vita-Salute San Raffaele, Milan, Italy.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: claudio.bordignon{at}hsr.it

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Polymeric micelles from poly(ethylene glycol)-poly(amino acid) block copolymer for drug and gene delivery.
K. Osada, R. J. Christie, and K. Kataoka (2009)
J R Soc Interface 6, S325-S339
   Abstract »    Full Text »    PDF »
Sustained high-level polyclonal hematopoietic marking and transgene expression 4 years after autologous transplantation of rhesus macaques with SIV lentiviral vector-transduced CD34+ cells.
Y.-J. Kim, Y.-S. Kim, A. Larochelle, G. Renaud, T. G. Wolfsberg, R. Adler, R. E. Donahue, P. Hematti, B.-K. Hong, J. Roayaei, et al. (2009)
Blood 113, 5434-5443
   Abstract »    Full Text »    PDF »
Long-term polyclonal and multilineage engraftment of methylguanine methyltransferase P140K gene-modified dog hematopoietic cells in primary and secondary recipients.
B. C. Beard, R. Sud, K. A. Keyser, C. Ironside, T. Neff, S. Gerull, G. D. Trobridge, and H.-P. Kiem (2009)
Blood 113, 5094-5103
   Abstract »    Full Text »    PDF »
Long-term outcome after hematopoietic stem cell transplantation of a single-center cohort of 90 patients with severe combined immunodeficiency.
B. Neven, S. Leroy, H. Decaluwe, F. Le Deist, C. Picard, D. Moshous, N. Mahlaoui, M. Debre, J.-L. Casanova, L. Dal Cortivo, et al. (2009)
Blood 113, 4114-4124
   Abstract »    Full Text »    PDF »
The Cellular Amount of the Common {gamma}-Chain Influences Spontaneous or Induced Cell Proliferation.
S. Amorosi, I. Russo, G. Amodio, C. Garbi, L. Vitiello, L. Palamaro, M. Adriani, I. Vigliano, and C. Pignata (2009)
J. Immunol. 182, 3304-3309
   Abstract »    Full Text »    PDF »
Successful Low-Risk Hematopoietic Cell Therapy in a Mouse Model of Type 1 Gaucher Disease.
I. B. Enquist, E. Nilsson, J.-E. Mansson, M. Ehinger, J. Richter, and S. Karlsson (2009)
Stem Cells 27, 744-752
   Abstract »    Full Text »    PDF »
Gene Therapy for Immunodeficiency Due to Adenosine Deaminase Deficiency.
A. Aiuti, F. Cattaneo, S. Galimberti, U. Benninghoff, B. Cassani, L. Callegaro, S. Scaramuzza, G. Andolfi, M. Mirolo, I. Brigida, et al. (2009)
N. Engl. J. Med. 360, 447-458
   Abstract »    Full Text »    PDF »
Gene Therapy Fulfilling Its Promise.
D. B. Kohn and F. Candotti (2009)
N. Engl. J. Med. 360, 518-521
   Full Text »    PDF »
Insertional Gene Activation by Lentiviral and Gammaretroviral Vectors.
M. Bokhoven, S. L. Stephen, S. Knight, E. F. Gevers, I. C. Robinson, Y. Takeuchi, and M. K. Collins (2009)
J. Virol. 83, 283-294
   Abstract »    Full Text »    PDF »
In vivo proliferation advantage of genetically corrected hematopoietic stem cells in a mouse model of Fanconi anemia FA-D1.
P. Rio, N. W. Meza, A. Gonzalez-Murillo, S. Navarro, L. Alvarez, J. Surralles, M. Castella, G. Guenechea, J. C. Segovia, H. Hanenberg, et al. (2008)
Blood 112, 4853-4861
   Abstract »    Full Text »    PDF »
Interfering RNA-mediated purine analog resistance for in vitro and in vivo cell selection.
C. C. Porter and J. DeGregori (2008)
Blood 112, 4466-4474
   Abstract »    Full Text »    PDF »
Hematopoietic stem cell transplantation: 40 years of continuous progress and evolution.
F. Porta, F. Locatelli, and G. R. Burgio (2008)
Haematologica 93, 1607-1610
   Full Text »    PDF »
Unaltered repopulation properties of mouse hematopoietic stem cells transduced with lentiviral vectors.
A. Gonzalez-Murillo, M. L. Lozano, E. Montini, J. A. Bueren, and G. Guenechea (2008)
Blood 112, 3138-3147
   Abstract »    Full Text »    PDF »
In vivo selection of genetically modified erythroblastic progenitors leads to long-term correction of {beta}-thalassemia.
A. Miccio, R. Cesari, F. Lotti, C. Rossi, F. Sanvito, M. Ponzoni, S. J. E. Routledge, C.-M. Chow, M. N. Antoniou, and G. Ferrari (2008)
PNAS 105, 10547-10552
   Abstract »    Full Text »    PDF »
Genetic Enhancement of Stem Cell Engraftment, Survival, and Efficacy.
M. S. Penn and A. A. Mangi (2008)
Circ. Res. 102, 1471-1482
   Abstract »    Full Text »    PDF »
Neonatal bone marrow transplantation of ADA-deficient SCID mice results in immunologic reconstitution despite low levels of engraftment and an absence of selective donor T lymphoid expansion.
D. A. Carbonaro, X. Jin, D. Cotoi, T. Mi, X.-J. Yu, D. C. Skelton, F. Dorey, R. E. Kellems, M. R. Blackburn, and D. B. Kohn (2008)
Blood 111, 5745-5754
   Abstract »    Full Text »    PDF »
DNA bar coding and pyrosequencing to analyze adverse events in therapeutic gene transfer.
G. P. Wang, A. Garrigue, A. Ciuffi, K. Ronen, J. Leipzig, C. Berry, C. Lagresle-Peyrou, F. Benjelloun, S. Hacein-Bey-Abina, A. Fischer, et al. (2008)
Nucleic Acids Res. 36, e49
   Abstract »    Full Text »    PDF »
Development of gene therapy for blood disorders.
A. W. Nienhuis (2008)
Blood 111, 4431-4444
   Abstract »    Full Text »    PDF »
Altered intracellular and extracellular signaling leads to impaired T-cell functions in ADA-SCID patients.
B. Cassani, M. Mirolo, F. Cattaneo, U. Benninghoff, M. Hershfield, F. Carlucci, A. Tabucchi, C. Bordignon, M. G. Roncarolo, and A. Aiuti (2008)
Blood 111, 4209-4219
   Abstract »    Full Text »    PDF »
An experimental system for the evaluation of retroviral vector design to diminish the risk for proto-oncogene activation.
B. Y. Ryu, M. V. Evans-Galea, J. T. Gray, D. M. Bodine, D. A. Persons, and A. W. Nienhuis (2008)
Blood 111, 1866-1875
   Abstract »    Full Text »    PDF »
Update on clinical gene therapy in childhood.
W. Qasim, H Bobby Gaspar, and A. J Thrasher (2007)
Arch. Dis. Child. 92, 1028-1031
   Abstract »    Full Text »    PDF »
Stable differentiation and clonality of murine long-term hematopoiesis after extended reduced-intensity selection for MGMT P140K transgene expression.
C. R. Ball, I. H. Pilz, M. Schmidt, S. Fessler, D. A. Williams, C. von Kalle, and H. Glimm (2007)
Blood 110, 1779-1787
   Abstract »    Full Text »    PDF »
Hot spots of retroviral integration in human CD34+ hematopoietic cells.
C. Cattoglio, G. Facchini, D. Sartori, A. Antonelli, A. Miccio, B. Cassani, M. Schmidt, C. von Kalle, S. Howe, A. J. Thrasher, et al. (2007)
Blood 110, 1770-1778
   Abstract »    Full Text »    PDF »
Lentiviral vectors containing an enhancer-less ubiquitously acting chromatin opening element (UCOE) provide highly reproducible and stable transgene expression in hematopoietic cells.
F. Zhang, S. I. Thornhill, S. J. Howe, M. Ulaganathan, A. Schambach, J. Sinclair, C. Kinnon, H. B. Gaspar, M. Antoniou, and A. J. Thrasher (2007)
Blood 110, 1448-1457
   Abstract »    Full Text »    PDF »
Stable reduction of CCR5 by RNAi through hematopoietic stem cell transplant in non-human primates.
D. S. An, R. E. Donahue, M. Kamata, B. Poon, M. Metzger, S.-H. Mao, A. Bonifacino, A. E. Krouse, J.-L. Darlix, D. Baltimore, et al. (2007)
PNAS 104, 13110-13115
   Abstract »    Full Text »    PDF »
Granulocyte Colony-Stimulating Factor Prior to Nonmyeloablative Irradiation Decreases Murine Host Hematopoietic Stem Cell Function and Increases Engraftment of Donor Marrow Cells.
C. Barese, N. Pech, S. Dirscherl, J. L. Meyers, A. L. Sinn, M. C. Yoder, W. S. Goebel, and M. C. Dinauer (2007)
Stem Cells 25, 1578-1585
   Abstract »    Full Text »    PDF »
Diamond-Blackfan anemia: erythropoiesis lost in translation.
J. Flygare and S. Karlsson (2007)
Blood 109, 3152-3154
   Abstract »    Full Text »    PDF »
Patients with adenosine deaminase deficiency surviving after hematopoietic stem cell transplantation are at high risk of CNS complications.
M. Honig, M. H. Albert, A. Schulz, M. Sparber-Sauer, C. Schutz, B. Belohradsky, T. Gungor, M. T. Rojewski, H. Bode, U. Pannicke, et al. (2007)
Blood 109, 3595-3602
   Abstract »    Full Text »    PDF »
Retroviral vector insertion sites associated with dominant hematopoietic clones mark "stemness" pathways.
O. S. Kustikova, H. Geiger, Z. Li, M. H. Brugman, S. M. Chambers, C. A. Shaw, K. Pike-Overzet, D. d. Ridder, F. J. T. Staal, G. v. Keudell, et al. (2007)
Blood 109, 1897-1907
   Abstract »    Full Text »    PDF »
Prolonged pancytopenia in a gene therapy patient with ADA-deficient SCID and trisomy 8 mosaicism: a case report.
B. C. Engel, G. M. Podsakoff, J. L. Ireland, E. M. Smogorzewska, D. A. Carbonaro, K. Wilson, A. Shah, N. Kapoor, M. Sweeney, M. Borchert, et al. (2007)
Blood 109, 503-506
   Abstract »    Full Text »    PDF »
The Yin and Yang of Stem Cell Gene Therapy: Insights into Hematopoiesis, Leukemogenesis, and Gene Therapy Safety.
C. E. Dunbar (2007)
Hematology 2007, 460-465
   Abstract »    Full Text »    PDF »
Ex vivo gene therapy with lentiviral vectors rescues adenosine deaminase (ADA)-deficient mice and corrects their immune and metabolic defects.
A. Mortellaro, R. J. Hernandez, M. M. Guerrini, F. Carlucci, A. Tabucchi, M. Ponzoni, F. Sanvito, C. Doglioni, C. D. Serio, L. Biasco, et al. (2006)
Blood 108, 2979-2988
   Abstract »    Full Text »    PDF »
Complete correction of murine Artemis immunodeficiency by lentiviral vector-mediated gene transfer.
G. Mostoslavsky, A. J. Fabian, S. Rooney, F. W. Alt, and R. C. Mulligan (2006)
PNAS 103, 16406-16411
   Abstract »    Full Text »    PDF »
Cell-culture assays reveal the importance of retroviral vector design for insertional genotoxicity.
U. Modlich, J. Bohne, M. Schmidt, C. von Kalle, S. Knoss, A. Schambach, and C. Baum (2006)
Blood 108, 2545-2553
   Abstract »    Full Text »    PDF »
Effective cell and gene therapy in a murine model of Gaucher disease.
I. B. Enquist, E. Nilsson, A. Ooka, J.-E. Mansson, K. Olsson, M. Ehinger, R. O. Brady, J. Richter, and S. Karlsson (2006)
PNAS 103, 13819-13824
   Abstract »    Full Text »    PDF »
Unique risk factors for insertional mutagenesis in a mouse model of XSCID gene therapy.
Y. Shou, Z. Ma, T. Lu, and B. P. Sorrentino (2006)
PNAS 103, 11730-11735
   Abstract »    Full Text »    PDF »
In Vitro Culture During Retroviral Transduction Improves Thymic Repopulation and Output After Total Body Irradiation and Autologous Peripheral Blood Progenitor Cell Transplantation in Rhesus Macaques.
K. Lore, R. Seggewiss, F. J. Guenaga, S. Pittaluga, R. E. Donahue, A. Krouse, M. E. Metzger, R. A. Koup, C. Reilly, D. C. Douek, et al. (2006)
Stem Cells 24, 1539-1548
   Abstract »    Full Text »    PDF »
Proteasome activity restricts lentiviral gene transfer into hematopoietic stem cells and is down-regulated by cytokines that enhance transduction.
F. R. Santoni de Sio, P. Cascio, A. Zingale, M. Gasparini, and L. Naldini (2006)
Blood 107, 4257-4265
   Abstract »    Full Text »    PDF »
Correction of canine X-linked severe combined immunodeficiency by in vivo retroviral gene therapy.
S. S. T.-D. Ravin, D. R. Kennedy, N. Naumann, J. S. Kennedy, U. Choi, B. J. Hartnett, G. F. Linton, N. L. Whiting-Theobald, P. F. Moore, W. Vernau, et al. (2006)
Blood 107, 3091-3097
   Abstract »    Full Text »    PDF »
Anatomical Compartments Modify the Response of Human Hematopoietic Cells to a Mitogenic Signal.
Y. Nagasawa, B. L. Wood, L. Wang, I. Lintmaer, W. Guo, T. Papayannopoulou, M. A. Harkey, C. Nourigat, and C. A. Blau (2006)
Stem Cells 24, 908-917
   Abstract »    Full Text »    PDF »
Increasing importance of stem cell gene therapy in adenosine deaminase deficiency?.
O. Ozdemir, E. Lainka, T. Niehues, and M. Hershfield (2006)
Clin. Vaccine Immunol. 13, 433-435
   Full Text »    PDF »
HOXB4-Induced Self-Renewal of Hematopoietic Stem Cells Is Significantly Enhanced by p21 Deficiency.
N. Miyake, A. C.M. Brun, M. Magnusson, K. Miyake, D. T. Scadden, and S. Karlsson (2006)
Stem Cells 24, 653-661
   Abstract »    Full Text »    PDF »
Survival of the fittest: in vivo selection and stem cell gene therapy.
T. Neff, B. C. Beard, and H.-P. Kiem (2006)
Blood 107, 1751-1760
   Abstract »    Full Text »    PDF »
Retroviral vector integration deregulates gene expression but has no consequence on the biology and function of transplanted T cells.
A. Recchia, C. Bonini, Z. Magnani, F. Urbinati, D. Sartori, S. Muraro, E. Tagliafico, A. Bondanza, M. T. L. Stanghellini, M. Bernardi, et al. (2006)
PNAS 103, 1457-1462
   Abstract »    Full Text »    PDF »
Long-term immune reconstitution in RAG-1-deficient mice treated by retroviral gene therapy: a balance between efficiency and toxicity.
C. Lagresle-Peyrou, F. Yates, M. Malassis-Seris, C. Hue, E. Morillon, A. Garrigue, A. Liu, P. Hajdari, D. Stockholm, O. Danos, et al. (2006)
Blood 107, 63-72
   Abstract »    Full Text »    PDF »
Isolating gene-corrected stem cells without drug selection.
S. Hatada, L. W. Arnold, T. Hatada, J. E. Cowhig Jr., D. Ciavatta, and O. Smithies (2005)
PNAS 102, 16357-16361
   Abstract »    Full Text »    PDF »
In vivo gene transfer into rat bone marrow progenitor cells using rSV40 viral vectors.
B. Liu, J. Daviau, C. N. Nichols, and D. S. Strayer (2005)
Blood 106, 2655-2662
   Abstract »    Full Text »    PDF »
Intrathymic administration of hematopoietic progenitor cells enhances T cell reconstitution in ZAP-70 severe combined immunodeficiency.
O. Adjali, R. R. Vicente, C. Ferrand, C. Jacquet, C. Mongellaz, P. Tiberghien, K. Chebli, V. S. Zimmermann, and N. Taylor (2005)
PNAS 102, 13586-13591
   Abstract »    Full Text »    PDF »
Improved transduction of human sheep repopulating cells by retrovirus vectors pseudotyped with feline leukemia virus type C or RD114 envelopes.
M. L. Lucas, N. E. Seidel, C. D. Porada, J. G. Quigley, S. M. Anderson, H. L. Malech, J. L. Abkowitz, E. D. Zanjani, and D. M. Bodine (2005)
Blood 106, 51-58
   Abstract »    Full Text »    PDF »
Clonal evidence for the transduction of CD34+ cells with lymphomyeloid differentiation potential and self-renewal capacity in the SCID-X1 gene therapy trial.
M. Schmidt, S. Hacein-Bey-Abina, M. Wissler, F. Carlier, A. Lim, C. Prinz, H. Glimm, I. Andre-Schmutz, C. Hue, A. Garrigue, et al. (2005)
Blood 105, 2699-2706
   Abstract »    Full Text »    PDF »
Recent developments in gene transfer: risk and ethics.
J. Kimmelman (2005)
BMJ 330, 79-82
   Full Text »    PDF »
Diminished Mobilization of Self-Inactivating (SIN) Lentiviral Vectors Containing Globin Regulatory Elements Compared to Those Containing a Retroviral Long Terminal Repeat..
H. Hanawa, D. A. Persons, T. Shimada, and A. W. Nienhuis (2004)
Blood (ASH Annual Meeting Abstracts) 104, 5271
   Abstract »
Recent developments and current status of gene therapy using viral vectors in the United Kingdom.
K. Relph, K. Harrington, and H. Pandha (2004)
BMJ 329, 839-842
   Full Text »    PDF »
XLA gene therapy turns a corner.
K. D. Bunting (2004)
Blood 104, 1236
   Full Text »    PDF »
The impact of low-dose busulfan on clonal dynamics in nonhuman primates.
K. Kuramoto, D. Follman, P. Hematti, S. Sellers, M. O. Laukkanen, R. Seggewiss, M. E. Metzger, A. Krouse, R. E. Donahue, C. von Kalle, et al. (2004)
Blood 104, 1273-1280
   Abstract »    Full Text »    PDF »
Efficient gene transfer into rhesus repopulating hematopoietic stem cells using a simian immunodeficiency virus-based lentiviral vector system.
H. Hanawa, P. Hematti, K. Keyvanfar, M. E. Metzger, A. Krouse, R. E. Donahue, S. Kepes, J. Gray, C. E. Dunbar, D. A. Persons, et al. (2004)
Blood 103, 4062-4069
   Abstract »    Full Text »    PDF »
Overexpression of CXCR4 on human CD34+ progenitors increases their proliferation, migration, and NOD/SCID repopulation.
J. Kahn, T. Byk, L. Jansson-Sjostrand, I. Petit, S. Shivtiel, A. Nagler, I. Hardan, V. Deutsch, Z. Gazit, D. Gazit, et al. (2004)
Blood 103, 2942-2949
   Abstract »    Full Text »    PDF »
Human CD34+ cells differentiate into microglia and express recombinant therapeutic protein.
M. Asheuer, F. Pflumio, S. Benhamida, A. Dubart-Kupperschmitt, F. Fouquet, Y. Imai, P. Aubourg, and N. Cartier (2004)
PNAS 101, 3557-3562
   Abstract »    Full Text »    PDF »
Capillary Electrophoresis in Diagnosis and Monitoring of Adenosine Deaminase Deficiency.
F. Carlucci, A. Tabucchi, A. Aiuti, F. Rosi, F. Floccari, R. Pagani, and E. Marinello (2003)
Clin. Chem. 49, 1830-1838
   Abstract »    Full Text »    PDF »
Defects in T-cell-mediated immunity to influenza virus in murine Wiskott-Aldrich syndrome are corrected by oncoretroviral vector-mediated gene transfer into repopulating hematopoietic cells.
T. S. Strom, S. J. Turner, S. Andreansky, H. Liu, P. C. Doherty, D. K. Srivastava, J. M. Cunningham, and A. W. Nienhuis (2003)
Blood 102, 3108-3116
   Abstract »    Full Text »    PDF »
LMO2-Associated Clonal T Cell Proliferation in Two Patients after Gene Therapy for SCID-X1.
S. Hacein-Bey-Abina, C. Von Kalle, M. Schmidt, M. P. McCormack, N. Wulffraat, P. Leboulch, A. Lim, C. S. Osborne, R. Pawliuk, E. Morillon, et al. (2003)
Science 302, 415-419
   Abstract »    Full Text »    PDF »
In vivo reversion to normal of inherited mutations in humans.
R Hirschhorn (2003)
J. Med. Genet. 40, 721-728
   Abstract »    Full Text »    PDF »
Successful treatment of murine {beta}-thalassemia using in vivo selection of genetically modified, drug-resistant hematopoietic stem cells.
D. A. Persons, E. R. Allay, N. Sawai, P. W. Hargrove, T. P. Brent, H. Hanawa, A. W. Nienhuis, and B. P. Sorrentino (2003)
Blood 102, 506-513
   Abstract »    Full Text »    PDF »
Lentivirus Vectors Incorporating the Immunoglobulin Heavy Chain Enhancer and Matrix Attachment Regions Provide Position-Independent Expression in B Lymphocytes.
C. Lutzko, D. Senadheera, D. Skelton, D. Petersen, and D. B. Kohn (2003)
J. Virol. 77, 7341-7351
   Abstract »    Full Text »    PDF »
Highly Efficient Lentiviral Gene Transfer in CD34+ and CD34+/38-/lin- Cells from Mobilized Peripheral Blood after Cytokine Prestimulation.
F. Geronimi, E. Richard, I. Redonnet-Vernhet, I. Lamrissi-Garcia, M. Lalanne, C. Ged, F. Moreau-Gaudry, and H. de Verneuil (2003)
Stem Cells 21, 472-480
   Abstract »    Full Text »    PDF »
Nonmyeloablative conditioning is sufficient to allow engraftment of EGFP-expressing bone marrow and subsequent acceptance of EGFP-transgenic skin grafts in mice.
G. Andersson, B. M. W. Illigens, K. W. Johnson, D. Calderhead, C. LeGuern, G. Benichou, M. E. White-Scharf, and J. D. Down (2003)
Blood 101, 4305-4312
   Abstract »    Full Text »    PDF »
Uses and abuses of genetic engineering.
D R Alexander (2003)
Postgrad. Med. J. 79, 249-251
   Full Text »    PDF »
Persistence and expression of the adenosine deaminase gene for 12 years and immune reaction to gene transfer components: long-term results of the first clinical gene therapy trial.
L. M. Muul, L. M. Tuschong, S. L. Soenen, G. J. Jagadeesh, W. J. Ramsey, Z. Long, C. S. Carter, E. K. Garabedian, M. Alleyne, M. Brown, et al. (2003)
Blood 101, 2563-2569
   Abstract »    Full Text »    PDF »
Side effects of retroviral gene transfer into hematopoietic stem cells.
C. Baum, J. Dullmann, Z. Li, B. Fehse, J. Meyer, D. A. Williams, and C. von Kalle (2003)
Blood 101, 2099-2113
   Abstract »    Full Text »    PDF »
Retroviral transduction efficiency of G-CSF+SCF-mobilized peripheral blood CD34+ cells is superior to G-CSF or G-CSF+Flt3-L-mobilized cells in nonhuman primates.
P. Hematti, S. E. Sellers, B. A. Agricola, M. E. Metzger, R. E. Donahue, and C. E. Dunbar (2003)
Blood 101, 2199-2205
   Abstract »    Full Text »    PDF »
Modulation of Coxsackie-Adenovirus Receptor Expression for Increased Adenoviral Transgene Expression.
A. Hemminki, A. Kanerva, B. Liu, M. Wang, R. D. Alvarez, G. P. Siegal, and D. T. Curiel (2003)
Cancer Res. 63, 847-853
   Abstract »    Full Text »    PDF »
Inhibiting HIV-1 infection in human T cells by lentiviral-mediated delivery of small interfering RNA against CCR5.
X.-F. Qin, D. S. An, I. S. Y. Chen, and D. Baltimore (2003)
PNAS 100, 183-188
   Abstract »    Full Text »    PDF »
Reprogramming Immune Responses: Enabling Cellular Therapies and Regenerative Medicine.
J. D. Down and M. E. White-Scharf (2003)
Stem Cells 21, 21-32
   Abstract »    Full Text »    PDF »
Immunodeficiency Disorders.
M. D. Cooper, L. L. Lanier, M. E. Conley, and J. M. Puck (2003)
Hematology 2003, 314-330
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)